Probe substrate and enzyme source-dependent inhibition of UDP-glucuronosyltransferase (UGT) 1A9 by wogonin
| Autor: | Pang Liqun, Gao Chengcheng, Yan Wei, Ma Tianheng, Xie Rui |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Glucuronosyltransferase
Glucuronidation Pharmacology chemistry.chemical_compound Wogonin Non-competitive inhibition In vivo Medicine Humans Enzyme Inhibitors Hymecromone biology Dose-Response Relationship Drug business.industry General Medicine Original Articles biology.organism_classification chemistry Flavanones UDP-Glucuronosyltransferase 1A9 Microsome biology.protein Microsomes Liver Scutellaria baicalensis Indicators and Reagents business |
| Zdroj: | African Health Sciences; Vol 13, No 3 (2013); 551-555 |
| ISSN: | 1680-6905 |
| Popis: | Background: Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R&D process of drugs or herbal ingredients.Objective: To evaluate the inhibition potential of wogonin (an important flavonoid isolated from the root of Scutellaria baicalensis) towards one of the most important phase II DMEs, UDP-glucuronosyltransferase (UGT) 1A9.Methods: Both recombinant UGT1A9-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and human liver microsomes (HLMs)-catalyzed propofol glucuronidation reaction were used as two different probe reactions.Results: Wogonin noncompetitively inhibited recombinant UGT1A9-catalyzed 4-MU glucuronidation, and exerted competitive inhibition towards HLMs-catalyzed propofol glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 3.2 ìM and 52.0ìM, respectively.Conclusion: Necessary monitoring was needed when wogonin was co-administered with the clinical drugs mainly undergoing UGT1A9-mediated glucuronidation elimination. Additionally, probe reactions-dependent inhibition of wogonin towards the activity of UGT1A9 should be paid attention when translating these in vitro data into in vivo situation.Keywords: wogonin, drug-drug interaction (DDI), UDP-glucuronosyltransferases (UGTs) |
| Databáze: | OpenAIRE |
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